1. Field of the Invention
The present invention relates to a compound which is represented by the following formula (Ia) or (Ib), and which can be used as an important intermediate for preparing β-lactam group antibiotics, and to a stereo-selective preparation method thereof.

2. Description of the Background Art
Compound A, B and C represented by the following formulae are important intermediates which can be used in preparing β-lactam group antibiotics.

As the importance of β-lactam group antibiotics (Angew. Chem., Int. Ed. Engl., 1985, 24, 180) has been increased, the compound C has been used as an important intermediate for preparing (1′R,3R)-4-acyloxy-3-(1′-hydroxy-ethyl)azetidin-2-one (compound A) which requires a stereochemical characteristics. Therefore, synthetic methods of the intermediate compound C have been spotlighted. Currently, preparation of compound A has been attempted with various chiral preparation units, namely, L-aspartamic acid (P. J. Reider, Tetrahedron Lett., 1982, 23, 2293), 2-benzamidomethyl-3-hydroxybutyrate (R. Noyori, J. Am. Chem. Soc., 1989, 111, 9134), (3R)-hydroxybutyrate (I. Sada, Eur. Pat. Appl. 280962 (Chem. Abstr., 1989, 110 (17), 154035s)) and the like. A preparation method through a classical resolution of racemic intermediates has been also attempted (M. Masayoshi, Eur. Pat. Appl. 421283 (Chem. Abstr, 1991, 115 (11), 1128442e)).
(1′R,3S)-3-(1′-t-butyldimethylsilyloxy)azetidin-2-one which is a derivative of the compound B has been known as a useful starting material for preparing β-lactam group antibiotics. It is because that all of commonly used penicillin antibiotics, cephalosporin antibiotics, carbapenem antibiotics which are expected to be antibiotics of the next generation and the like have an azetidin-2-one skeleton.
As a preparation method of (1′R,3S)-3-(1′-t-butyldimethylsilyloxy)azetidin-2-one, there has been reported a method of Noyori et al. (J. Am. Chem. Soc. 111, 9134, 1989; and Japan Patent No. 2134349), and a method of a pharmaceutical company in Swiss (U.S. Pat. No. 4,927,507).
The method of Noyori et al. is performed by introducing asymmetric hydrogen to 2-amidomethyl acetoacetate ester, hydrolyzing with an acid to lactamize, and then performing silylation. The method of Noyori et al. uses a stereoselective hydrogenation reaction. However, since an amide is used as a starting material, a strong acid must be used in hydrolysis, and since protection of hydroxy group is performed after the lactamization, it is difficult to perform the lactamization. Besides, separation and purification processes are complicated.
The method of a pharmaceutical company in Swiss comprises sequential steps of a reduction of 2-amidomethyl acetoacetate ester with yeast to obtain a 2-amidomethyl-3-hydroxy butanoic acid ester, a substitution of 2-amidomethyl-3-hydroxy butanoic acid ester into a 5,6-dihydro-(1H,3H,4H)-oxazinyl-5-carboxylic acid ester derivative, an isomerization so as to have a desirable stereochemistry, hydrolysis, lactamization and silylation. However, this method does not seem to be practical in that the obtained product may be hydrolyzed because diasteromers are separated after introducing 2-amidomethyl-3-hydroxy butanoic acid ester into 5,6-dihydro-(1H,3H,4H)-oxazinyl-5-carbonic acid ester derivative, procedures of separation and purification of diastereomers are also complicated, and it has too many steps.
The compound B can be also prepared from a α-substituted β-hydroxy ester, such as the compound C, and the compound C can be prepared from a α-substituted β-keto ester.
As described above, since the compounds A and B can be used as important intermediates for preparing of β-lactam group antibiotics and can be prepared from the compound C, it is necessary to provide a preparation method of the compound C.
Recently, there have been continuous attempts to selectively synthesize an optical isomer which exhibits a useful biological activity among racemic compounds. To achieve this purpose, there have been developed a method using biological catalyst which is different from the conventional organic-chemical preparation method. The preparation method using the biological catalyst is advantageous in that it is more convenient than the conventional organic-chemical preparation method, and it is not necessary to use a poisonous chemical reagent.
Biological catalysis is spotlighted because of its stereoselectivity including an optical isomeric or diastereomeric selectivity. Therefore, a reaction using an enzyme is a very useful experimental method for preparing optically pure compounds. Particularly, a reaction using Baker's Yeast (BY) has been generally used in reduction of carbonyl compounds. However, according to a recently disclosed preparation method, it has been reported that the reduction of a carbonyl group of β-keto ester using Baker's Yeast (BY) generally generates (S)-3-hydroxy compound (S. Servi, Synthesis, 1990, 1; R. Csuk, Chem. Rev., 1991, 91, 49). That is, there have not been reported any preparation methods of a (R)-3-hydroxy compound by reducing the carbonyl group of β-keto ester.